Swanson James M, Moyzis Robert K, McGough James J, McCracken James T, Riddle Mark A, Kollins Scott H, Greenhill Laurence L, Abikoff Howard B, Wigal Tim, Wigal Sharon B, Posner Kelly, Skrobala Anne M, Davies Mark, Ghuman Jaswinder K, Cunningham Charles, Vitiello Benedetto, Stehli Annamarie, Smalley Susan L, Grady Deborah
Child Development Center, University of California-Irvine, 19722 MacArthur Boulevard, Irvine, CA 92612, USA.
J Child Adolesc Psychopharmacol. 2007 Oct;17(5):635-46. doi: 10.1089/cap.2007.0076.
In children diagnosed with attention-deficit/hyperactivity disorder (ADHD) and their parents, who were participants of the Preschool ADHD Treatment Study (PATS), we assessed the effect of source of DNA (from buccal or blood cells) on the genotyping success rate and allele percentages for the five polymorphisms in three candidate genes (DAT1, DRD4, and SNAP 25) investigated in the PATS pharmacogenetic study of response to stimulant medication.
At baseline assessment, 241 individuals (113 probands and 128 parents) consented to participate; 144 individuals (52 probands and 92 parents) provided blood samples from venipuncture, and 97 individuals (61 probands and 36 parents) provided buccal samples from cheek swab as specimens for isolation of DNA. Three types of polymorphisms-variable number of tandem repeat (VNTR) polymorphism, tandem duplication polymorphism (TDP), and single nucleotide polymorphism (SNP)-were evaluated, including the DRD4 gene 48-bp VNTR in exon III, the DAT1 gene 40-bp VNTR in 3'-untranslated region, the DRD4 gene TDP 120-bp duplication in the promoter region, the SNAP-25 gene TC-1069 SNP, and the SNAP-25 gene TG-1065 SNP. Standard procedures were used to genotype individuals for each of these five polymorphisms.
Using the methods available in 2004, the genotyping success rate was on the average much greater for DNA from blood cells than buccal cells (e.g., 91% vs. 54% in probands). For some polymorphisms (DRD4-VNTR, DRD4-TDP, and SNAP25-TC SNP), allele proportion also varied by blood versus buccal source of DNA (e.g., 26.5% vs. 18.6% for the 7-repeat allele of the DRD4 gene).
The much lower success rate for genotyping based on DNA from buccal than blood cells is likely due to the quality of DNA derived from these two sources. The observed source differences in allele proportion may be due to self-selection related to choice of how specimens were collected (from cheek swab or venipuncture), or to a selective detection of some alleles based on differences in DNA quality.
在被诊断为注意力缺陷多动障碍（ADHD）的儿童及其父母（他们是学龄前ADHD治疗研究[PATS]的参与者）中，我们评估了DNA来源（来自颊细胞或血细胞）对PATS中关于兴奋剂药物反应的药物遗传学研究中所调查的三个候选基因（DAT1、DRD4和SNAP 25）的五个多态性的基因分型成功率和等位基因百分比的影响。
在基线评估时，241名个体（113名先证者和128名父母）同意参与；144名个体（52名先证者和92名父母）通过静脉穿刺提供血样，97名个体（61名先证者和36名父母）通过颊拭子提供颊部样本作为分离DNA的标本。评估了三种类型的多态性——串联重复可变数目多态性（VNTR）、串联重复多态性（TDP）和单核苷酸多态性（SNP），包括DRD4基因外显子III中的48 bp VNTR、DAT1基因3'非翻译区中的40 bp VNTR、DRD4基因启动子区中的120 bp TDP重复、SNAP - 25基因的TC - 1069 SNP以及SNAP - 25基因的TG - 1065 SNP。使用标准程序对这五个多态性中的每一个进行个体基因分型。
使用2004年可用的方法，血细胞来源的DNA的基因分型成功率平均比颊细胞来源的DNA高得多（例如，先证者中分别为91%和54%）。对于某些多态性（DRD4 - VNTR、DRD4 - TDP和SNAP2S - TC SNP），等位基因比例也因DNA的血液来源与颊部来源而异（例如，DRD4基因7重复等位基因分别为26.5%和18.6%）。
基于颊细胞DNA的基因分型成功率远低于血细胞DNA，这可能是由于这两种来源的DNA质量所致。观察到的等位基因比例的来源差异可能是由于与标本采集方式（颊拭子或静脉穿刺）的选择相关的自我选择，或者是由于基于DNA质量差异对某些等位基因的选择性检测。
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